目的 采用正交试验法优化硝基卡因的直接酯化工艺。方法 以对硝基苯甲酸和N,N-二乙氨基乙醇为原料，通过直接酯化法合成硝基卡因，选择反应的催化剂、溶剂、投料比、时间为考察因素，采用L9(34)正交试验确定硝基卡因的直接酯化法最佳工艺。结果 最佳工艺条件是催化剂为甲酸，溶剂为二甲苯，投料比为1∶1.10，反应时间为6 h。最佳工艺条件下的合成收率为98.17%，硝基卡因的质量分数为99.40%。结论 该合成硝基卡因的方法具有收率高、工艺简单、稳定可行的特点。

Objective To optimize the direct esterification prochyl p-nitrobenzoate by orthogonal test. Methods P-nitrobenzoic acid and N,N-diethyl amino ethanol were used as starting materials to synthesize the target compound by direct esterification process. Taking catalyst, solvent, the molar ratio of starting materials and reaction time as investigation factors, the best direct esterification process of diethylaminoethyl p-nitrobenzoate was determined by L9(34) orthogonal test. Results The optimal direct esterification process conditions were as follows: catalyst of formic acid, solvent of xylene, the molar ratio of 1∶1.10, and reaction time of 6 h. The yield of the optimal direct esterification process was 98.17%, and the purity of diethylaminoethyl p-nitrobenzoate was 99.40%. Conclusion The optimal direct esterification process for p-nitrobenzoate has the characteristics of high yield, simple process, stable and feasible.

北京中医药大学校级课题（2013-JYBZZ-JS-033）